The median follow-up for the entire cohort (n= 40,520) was 9 years, and the majority of patients were from western states. Most of the patients were diagnosed with stage I (80%), followed by stage II (12.6%), stage III (4.8%) and stage IV (2.6%) disease. There was a larger proportion of older patients (≥ 50 years) in the stages II and IV cohorts than in the stages I and III cohorts (69.8% and 71.9% v 51% and 52.4%, respectively, P < 0.001). About two-thirds of the stage IV patients were male, and there were more African American (2.5%) patients in the stage IV group than in the other three less advanced stage groups (0.4% for stage I, and 1% for stages II and III). Nodular melanoma was more commonly noted in patients with stages II (33.5%) and III (24.4%) disease, while superficial spreading melanoma was the predominant histologic subtype in the stage I group (50.9%). About two-thirds of stages I and II patients received treatment in the form of wide local excision (WLE) and/or sentinel node biopsy (SNB), while over 70% percent of the stage III patients underwent lymph node dissection (LND). For those with stage IV disease, radiation therapy was more often used (33.9%) than in the other three stage-specific cohorts.
depicts the traditional DSS curves for patients in this cohort with stages I through IV melanoma. The 10-year DSS estimates were 94.3% (95% CI: 94.0 – 94.6) for stage I, 61.5% (95% CI: 59.9–63.1) for stage II, 44.1% (95% CI: 41.4–46.7) for stage III, and 16.1% (95% CI: 12.7–19.7) for stage IV. In terms of traditional overall survival, the 10-year survival estimates were 83.0% (95% CI: 82.5 – 83.5) for stage I, 45.0% (95% CI: 43.5–46.6) for stage II, 36.5% (95% CI: 34.0–39.0) for stage III, and 9.1% (95% CI: 7.0–11.6) for stage IV ().
Figure 1A: Traditional Kaplan-Meier estimate of Melanoma Disease-Specific Survival at the time of diagnosis stratified by disease stage.
Stage-specific 5-year disease-specific melanoma CS is presented as a bar graph in . For patients with stage I melanoma, 5-year CS estimates remained constant over time at 97%, reflecting the high likelihood of cure at the time of diagnosis. For patients with stage II melanoma, 5-year CS estimates increased over time, from 72% at time 0 (diagnosis) to 86% for patients surviving 5 years. With more advanced melanoma (stages III and IV), there were even greater changes in 5-year CS over time. For patients with stage III disease, 5-year CS estimates increased from 51% at time 0 to 87% for survivors at 5 years. Five-year CS estimates for patients with Stage IV melanoma also improved dramatically for survivors over time, from 19% at time 0 to 84% for survivors at 5 years (). Similar trends were found for 5-year overall CS (). For example, 5-year CS estimates increased from 46% at time 0 to 80% for stage III survivors at 5 years.
Figure 2A–B: Melanoma-specific (A) and Overall (B) 5-year Conditional Survival estimates stratified by disease stage. Error bars represent the standard error.
The Cox proportional hazards model was used to identify prognostic factors associated with DSS for stages I to IV melanoma patients (). For stage I, the model demonstrated that age, gender, race, marital status, anatomic tumor location, and tumor histology were all significant prognostic factors. For stages II and III, all aforementioned variables except race were significant. While for stage IV, only age, marital status, and anatomic tumor location were statistically significantly associated with DSS.
Stage-specific multivariate Cox regression on disease-specific survival for melanoma patients (n=40,520) from SEER (1988–2000)
To account for their covariate influences on the survival function, additional CS estimates were adjusted for age, gender, race, marital status, anatomic tumor location, and tumor histology. The adjusted CS was calculated for subgroups of patients further stratified by age. through are generated from the adjusted survival function for these two age groups from each stage cohort, while controlling for the influence of above covariates. Overall, patients who were less than 50 years of age had much higher estimated survival at the time of diagnosis compared to patients who were 50 years of age or older. The differences between melanoma-specific survival at the time of diagnosis were 1% (stage I), 10% (stage II), 16% (stage III), and 9% (stage IV). In terms of CS, younger patients tended to have better outcomes, and of note, these age-related differences in CS generally diminished over time for the stages II and III cohorts.
Figure 3A–D. Stages I–IV Melanoma-specific 5-year Adjusted Conditional Survival stratified by age (≥50 v <50). Error bars represent the standard error. (A: stage I; B: stage II; C: stage III; D: stage IV)
When stage-specific subgroups were stratified by gender, males were noted to have lower 5-year melanoma-specific survival than females at the time of diagnosis (stage I: 96% v 97%, stage II: 69% v 78%, stage III: 48% v 56%, and stage IV: 17% v 20%, respectively). The CS estimates for both genders increased over time for each year of follow-up; specifically, at year 5, CS for males and females was 98% v 98% for stage I, 83% v 88% for stage II, 85% v 88% for stage III, and 82% v 83% for stage IV patients, respectively.
We also examined the impact of race, anatomic tumor location, and histology on stage-specific melanoma CS, and differing patterns emerged across disease stage groups. Because of the favorable prognosis for all patients with stage I melanoma, there were no major differences in CS among patients when stratified by race, tumor location, and histology. However, for the stages II–IV cohorts, we observed that the effects of race, anatomic tumor location, and histology decreased over time for stage-specific melanoma CS over time. For example, 5-year survival estimates for Caucasian patients with stage IV melanoma were lower than estimates for stage IV non-Caucasians by 9% at the time of diagnosis (18% v 27%) and by 4% at year 5 (82% v 86%), demonstrating a trend that race-related differences in CS decreased over time (p=0.06). In terms of histologic subtype, acral lentiginous melanomas were associated with worse CS than the superficial and nodular groups, regardless of the length of follow-up. But this subgroup always had the largest gain in CS over the 5 year follow-up period for stages I–III patients (improvements of 3%, 16%, and 40% for stages I, II, and III, respectively). With respect to tumor location, stages I–III patients who had primary tumors in the upper extremity were noted to have the most favorable CS, followed by the lower extremity, head/neck, and truncal groups, while stage IV patients who had primary tumors in the lower extremity had the highest CS among different locations
By testing whether the trends of the survival curves were different among various subgroups (i.e. age, race, sex, histology, and tumor location), in other words, we found that sex and histology were determinates of CS improvement for stages I, age, sex, and location for stage II, age, sex and histology for stage III patients (all p-values ≤0.05), and that none of the variables were determinates of CS improvement for the stage IV cohort.